Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of the blastocyst and can be maintained in the pluripotent state in defined conditions in both human and mouse. ES cells can theoretically be differentiated into every somatic and germ cell type. The development of appropriate conditions to differentiate ES cells into a variety of cell types and tissues therefore holds major promise for future cell replacement therapy. Pluripotent cells may also be obtained by reprogramming adult somatic cells into a pluripotent state (e.g., induced pluripotent stem cells, or iPS cells), providing a path for the generation of patient-specific pluripotent cells, which would overcome rejection problems associated with transplantation of ES cell-derived tissues.
Development begins with the process of gastrulation, during which undifferentiated cells from the inner cell mass of the blastocyst differentiate into the three germ layers from which all tissues of the body are generated. Ectoderm gives rise to skin and its appendages, the nervous system, and adrenal tissues. Mesoderm develops into the genito-urinary system, connective tissue, muscle, bone, cartilage, blood vessels, blood and heart. Endoderm produces the intestine, liver, pancreas, esophagus, trachea, lung and the pharyngeal apparatus, which is derived from the most anterior foregut endoderm.
Complex patterning processes along the dorsoventral, anteroposterior and left-right axis of the embryo occur, leading to the definition of specific domains in these germ layers that will later on give rise to specific tissues and organs. Patterning is accompanied by complex molecular changes. It therefore appears critical that to obtain enriched or pure and functional populations of mature cells, developmental cues need to be sequentially applied to guide the differentiation of pluripotent cells in vitro.